This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In order to generate a properly patterned organism, embryonic cells must integrate multiple signaling inputs that govern proliferation, differentiation, polarity, and motility. Many critical factors that regulate patterning of cells or tissues during development promote tumorigenesis and metastasis when misregulated postembryonically. Understanding how cells make decisions about when and where to migrate, and whether to differentiate or remain plastic, is the main goal of our project, and will provide insight into the general mechanisms coordinating cell fate and motility during development and oncogenesis. During vertebrate development, tissues of the posterior body are derived from a population of multipotent progenitor cells called the tailbud. Fate specification, differentiation, and cell migration are carefully coordinated within the tailbud to ensure that, as some cells exit the tailbud and become committed to specific fates, other cells are retained in the tailbud as undifferentiated precursors to support later tail outgrowth. Very little is known about how these processes are coordinated, however. We have found that misregulation of a Rho GTPase Activating Protein (GAP) called ARHGAP10, in conjuction with components of a noncanonical Wnt pathway that regulates cell movements in the embryo, causes pluripotent tailbud cells to mislocalize and direct the formation of a secondary tail. Loss of BMP activity has previously been shown to result in a similar phenotype, suggesting that multiple signaling inputs are required to restrict multipotent tailbud cells to only their appropriate location in the embryo. To begin an analysis of this process, we will: 1) Test genetic interactions between previously identified components to gain insight into how these signaling inputs are coordinated;we will assess the potential role of additional genes that also regulate cell migration;2) Test the hypothesis that ARHGAP10 functions through regulation of a RhoGTPase, specifically RhoA or Cdc42 by determining if modulating the activity of either protein affects this process;and 3) Use in vivo cell labeling and imaging techniques to determine the cellular basis of the defect-which cells are involved, and how do they get to their ectopic location, and then to test the hypothesis, suggested by studies of human ARHGAP10, that zebrafish ARHGAP10 promotes adhesion among tailbud cells by regulating the assembly or function of adherens junctions.